Effect of Repeated Low-level Red Light on Myopia Prevention Among Children in China With Premyopia: A Randomized Clinical Trial.

Importance: Myopia is a global concern, but effective prevention measures remain limited. Premyopia is a refractive state in which children are at higher risk of myopia, meriting preventive interventions. Objective: To assess the efficacy and safety of a repeated low-level red-light (RLRL) intervention in preventing incident myopia among children with premyopia. Design, Setting, and Participants: This was a 12-month, parallel-group, school-based randomized clinical trial conducted in 10 primary schools in Shanghai, China. A total of 139 children with premyopia (defined as cycloplegic spherical equivalence refraction [SER] of -0.50 to 0.50 diopter [D] in the more myopic eye and having at least 1 parent with SER ≤-3.00 D) in grades 1 to 4 were enrolled between April 1, 2021, and June 30, 2021; the trial was completed August 31, 2022. Interventions: Children were randomly assigned to 2 groups after grade stratification. Children in the intervention group received RLRL therapy twice per day, 5 days per week, with each session lasting 3 minutes. The intervention was conducted at school during semesters and at home during winter and summer vacations. Children in the control group continued usual activities. Main Outcomes and Measures: The primary outcome was the 12-month incidence rate of myopia (defined as SER ≤-0.50 D). Secondary outcomes included the changes in SER, axial length, vision function, and optical coherence tomography scan results over 12 months. Data from the more myopic eyes were analyzed. Outcomes were analyzed by means of an intention-to-treat method and per-protocol method. The intention-to-treat analysis included participants in both groups at baseline, while the per-protocol analysis included participants in the control group and those in the intervention group who were able to continue the intervention without interruption by the COVID-19 pandemic. Results: There were 139 children (mean [SD] age, 8.3 [1.1] years; 71 boys [51.1%]) in the intervention group and 139 children (mean [SD] age, 8.3 [1.1] years; 68 boys [48.9%]) in the control group. The 12-month incidence of myopia was 40.8% (49 of 120) in the intervention group and 61.3% (68 of 111) in the control group, a relative 33.4% reduction in incidence. For children in the intervention group who did not have treatment interruption secondary to the COVID-19 pandemic, the incidence was 28.1% (9 of 32), a relative 54.1% reduction in incidence. The RLRL intervention significantly reduced the myopic shifts in terms of axial length and SER compared with the control group (mean [SD] axial length, 0.30 [0.27] mm vs 0.47 [0.25] mm; difference, 0.17 mm [95% CI, 0.11-0.23 mm]; mean [SD] SER, -0.35 [0.54] D vs -0.76 [0.60] D; difference, -0.41 D [95% CI, -0.56 to -0.26 D]). No visual acuity or structural damage was noted on optical coherence tomography scans in the intervention group. Conclusions and Relevance: In this randomized clinical trial, RLRL therapy was a novel and effective intervention for myopia prevention, with good user acceptability and up to 54.1% reduction in incident myopia within 12 months among children with premyopia. Trial Registration: ClinicalTrials.gov Identifier: NCT04825769.

Interference of nuclear wavepackets in a pair of proton transfer reactions.

Quantum mechanics revolutionized chemists' understanding of molecular structure. In contrast, the kinetics of molecular reactions in solution are well described by classical, statistical theories. To reveal how the dynamics of chemical systems transition from quantum to classical, we study femtosecond proton transfer in a symmetric molecule with two identical reactant sites that are spatially apart. With the reaction launched from a superposition of two local basis states, we hypothesize that the ensuing motions of the electrons and nuclei will proceed, conceptually, in lockstep as a superposition of probability amplitudes until decoherence collapses the system to a product. Using ultrafast spectroscopy, we observe that the initial superposition state affects the reaction kinetics by an interference mechanism. With the aid of a quantum dynamics model, we propose how the evolution of nuclear wavepackets manifests the unusual intersite quantum correlations during the reaction.

Exciton Diffusion and Annihilation in an sp2 Carbon-Conjugated Covalent Organic Framework.

To optimize the optical and optoelectronic functionalities of two-dimensional (2D) covalent organic frameworks (COFs), detailed properties of emissive and nonradiative pathways after photoexcitation need to be elucidated and linked to particular structural designs. Here, we use transient absorption (TA) spectroscopy to study the colloidal suspension of the full sp2 carbon-conjugated sp2c-COF and characterize the spatial extent and diffusion dynamics of the emissive excitons generated by impulsive photoexcitation. The ∼3.5 Šstacking distance between 2D layers results in cofacial pyrene excitons that diffuse through the framework, while the state that dominates the emissive spectrum of the polycrystalline solid is assigned to an extended cofacial exciton whose 2D delocalization is promoted by C═C linkages. The subnanosecond kinetics of a photoinduced absorption (PIA) signal in the near-infrared, attributed to a charge-separated exciton, or polaron pair, reflects three-dimensional (3D) exciton diffusion as well as long-range exciton-exciton annihilation driven by resonance interactions. Within our experimental regime, doubling the excitation intensity results in a 10-fold increase in the estimated exciton diffusion length, from ∼3 to ∼30 nm, suggesting that higher lattice temperature may enhance exciton mobility in the COF colloid.

Coherent Two-Dimensional and Broadband Electronic Spectroscopies.

Over the past few decades, coherent broadband spectroscopy has been widely used to improve our understanding of ultrafast processes (e.g., photoinduced electron transfer, proton transfer, and proton-coupled electron transfer reactions) at femtosecond resolution. The advances in femtosecond laser technology along with the development of nonlinear multidimensional spectroscopy enabled further insights into ultrafast energy transfer and carrier relaxation processes in complex biological and material systems. New discoveries and interpretations have led to improved design principles for optimizing the photophysical properties of various artificial systems. In this review, we first provide a detailed theoretical framework of both coherent broadband and two-dimensional electronic spectroscopy (2DES). We then discuss a selection of experimental approaches and considerations of 2DES along with best practices for data processing and analysis. Finally, we review several examples where coherent broadband and 2DES were employed to reveal mechanisms of photoinitiated ultrafast processes in molecular, biological, and material systems. We end the review with a brief perspective on the future of the experimental techniques themselves and their potential to answer an even greater range of scientific questions.

Application of low level red light in myopia and amblyopia in children and adolescents / 中国学校卫生

Abstract@#Low level light therapy utilizes the photochemical effect of red light to induce reactions in the irradiated body tissue to achieve the therapeutic effect. Myopia and amblyopia are diseases which threaten the eye health of children and adolescents. Red light has been used to treat amblyopia for decades. Recently, its application in myopia prevention and control has become a new hotspot. This review summarizes the application of low level red light in children and adolescents with myopia and amblyopia from the aspects of intervention mode, effect, factors, mechanism and safety to provide reference for future researches.

Application of low level red light in myopia and amblyopia in children and adolescents / 中国学校卫生

Abstract@#Low level light therapy utilizes the photochemical effect of red light to induce reactions in the irradiated body tissue to achieve the therapeutic effect. Myopia and amblyopia are diseases which threaten the eye health of children and adolescents. Red light has been used to treat amblyopia for decades. Recently, its application in myopia prevention and control has become a new hotspot. This review summarizes the application of low level red light in children and adolescents with myopia and amblyopia from the aspects of intervention mode, effect, factors, mechanism and safety to provide reference for future researches.

Amplifying the reactivity of BODIPY photoremovable protecting groups.

Conjugated polymer nanoparticles (CPNs or Pdots) are used to sensitize the photorelease reaction of a BODIPY photoremovable protecting group. Sensitization yields effective values of ελΦpr - the product of the extinction coefficient at the irradiation wavelength and the photorelease quantum yield - that are more than 60-fold greater than those measured upon direct excitation.

Niclosamide inhibits vascular smooth muscle cell proliferation and migration and attenuates neointimal hyperplasia in injured rat carotid arteries.

BACKGROUND AND PURPOSE: The anti-helminthic drug niclosamide regulates multiple cellular signals including STAT3, AMP-activated protein kinase (AMPK), Akt, Wnt/ß-catenin and mitochondrial uncoupling which are involved in neointimal hyperplasia. Here we have examined the effects of niclosamide on vascular smooth muscle cell proliferation, migration and neointimal hyperplasia and assessed the potential mechanisms. EXPERIMENTAL APPROACH: Cell migration was measured by using wound-induced migration assay and Boyden chamber assay. Protein levels were measured by using Western blot technique. Neointimal hyperplasia in vivo was induced in rats by balloon injury to the carotid artery. KEY RESULTS: Niclosamide treatment inhibited serum-induced (15% FBS) and PDGF-BB-induced proliferation and migration of vascular smooth muscle cells (A10 cells). Niclosamide showed no cytotoxicity at anti-proliferative concentrations, but induced cell apoptosis at higher concentrations. Niclosamide treatment inhibited serum-induced (15% FBS) and PDGF-BB-induced STAT3 activation (increased protein levels of p-STAT3 at Tyr705 ) but activated AMPK, in A10 cells. Niclosamide exerted no significant effects on ß-catenin expression and the activities of ERK1/2 and Akt in A10 cells. Injection (i.p.) of soluble pegylated niclosamide (PEG5000-niclosamide) (equivalent to niclosamide 25 mg·kg-1 ) attenuated neointimal hyperplasia following balloon-injury in rat carotid arteries in vivo. CONCLUSIONS AND IMPLICATIONS: Niclosamide inhibited vascular smooth muscle cell proliferation and migration and attenuated neointimal hyperplasia in balloon-injured rat carotid arteries through a mechanism involving inhibition of STAT3.

Mitochondrial uncoupler triclosan induces vasorelaxation of rat arteries.

Our previous studies found that mitochondrial uncouplers induced vasodilation. Triclosan, the broad spectrum antibacterial agent, is the active ingredient in soaps and toothpastes. It was reported that triclosan induced mitochondrial uncoupling, so we aim to investigate the effects of triclosan on vascular function of rat mesenteric arteries and aorta. The isometric tension of rat mesenteric artery and thoracic aorta was recorded by multi-wire myograph system. The cytosolic [Ca2+]i, mitochondrial reactive oxygen species (mitoROS), and mitochondrial membrane potential of smooth muscle cells (A10 cells) were measured using laser scanning confocal microscopy. Triclosan treatment relaxed phenylephrine (PE)- and high K+ (KPSS)-induced constriction, and pre-treatment with triclosan inhibited PE- and KPSS-induced constriction of rat mesenteric arteries. In rat thoracic aorta, triclosan also relaxed PE- and KPSS-induced constriction. Triclosan induces vasorelaxation without involving KATP channel activation in smooth muscle cells of arteries. Triclosan treatment increased cytosolic [Ca2+]i, mitochondrial ROS production and depolarized mitochondrial membrane potential in A10 cells. In conclusion, triclosan induces mitochondrial uncoupling in vascular smooth muscle cells and relaxes the constricted rat mesenteric arteries and aorta of rats. The present results suggest that triclosan would indicate vasodilation effect if absorbed excessively in vivo.

Mitochondrial Fission Inhibitors Suppress Endothelin-1-Induced Artery Constriction.

BACKGROUND/AIMS: Endothelin-1 is implicated in the pathogenesis of hypertension, but the underlying mechanisms remained elusive. Our previous study found that inhibition of mitochondrial fission of smooth muscle cells suppressed phenylephrine- and high K+-induced artery constriction. Here, we studied the effects of mitochondrial fission inhibitors on endothelin-1-induced vasoconstriction. METHODS: The tension of rat mesenteric arteries and thoracic aorta was measured by using a multi-wire myograph system. Mitochondrial morphology of aortic smooth muscle cells was observed by using transmission electron microscopy. RESULTS: Dynamin-related protein-1 selective inhibitor mdivi-1 relaxed endothelin-1-induced constriction, and mdivi-1 pre-treatment prevented endothelin-1-induced constriction of rat mesenteric arteries with intact and denuded endothelium. Mdivi-1 had a similar inhibitory effect on rat thoracic aorta. Another mitochondrial fission inhibitor dynasore showed similar effects as mdivi-1 in rat mesenteric arteries. Mdivi-1 inhibited endothelin-1-induced increase of mitochondrial fission in smooth muscle cells of rat aorta. Rho-associated protein kinase inhibitor Y-27632 which relaxed endothelin-1-induced vasoconstriction inhibited endothelin-1-induced mitochondrial fission in smooth muscle cells of rat aorta. CONCLUSION: Endothelin-1 increases mitochondrial fission in vascular smooth muscle cells, and mitochondrial fission inhibitors suppress endothelin-1-induced vasoconstriction.

Arterial relaxation is coupled to inhibition of mitochondrial fission in arterial smooth muscle cells: comparison of vasorelaxant effects of verapamil and phentolamine.

Mitochondria are morphologically dynamic organelles which undergo fission and fusion processes. Our previous study found that arterial constriction was always accompanied by increased mitochondrial fission in smooth muscle cells, whereas inhibition of mitochondrial fission in smooth muscle cells was associated with arterial relaxation. Here, we used the typical vasorelaxants, verapamil and phentolamine, to further confirm the coupling between arterial constriction and mitochondrial fission in rat aorta. Results showed that phentolamine but not verapamil induced vasorelaxation in phenylephrine (PE)-induced rat thoracic aorta constriction. Verapamil, but not phentolamine, induced vasorelaxation in high K+ (KPSS)-induced rat thoracic aorta constriction. Pre-treatment with phentolamine prevented PE- but not KPSS-induced aorta constriction and pre-treatment with verapamil prevented both PE- and KPSS-induced aorta constriction. Transmission electron microscopy (TEM) results showed that verapamil but not phentolamine inhibited KPSS-induced excessive mitochondrial fission in aortic smooth muscle cells, and verapamil prevented both PE- and KPSS-induced excessive mitochondrial fission in aortic smooth muscle cells. Verapamil inhibited KPSS-induced excessive mitochondrial fission in cultured vascular smooth muscle cells (A10). These results further demonstrate that arterial relaxation is coupled to inhibition of mitochondrial fission in arterial smooth muscle cells.

Niclosamide ethanolamine inhibits artery constriction.

We previously demonstrated that the typical mitochondrial uncoupler carbonyl cyanide m-chlorophenylhydrazone (CCCP) inhibited artery constriction, but CCCP was used only as a pharmacological tool. Niclosamide is an anthelmintic drug approved by FDA. Niclosamide ethanolamine (NEN) is a salt form of niclosamide and has been demonstrated to uncouple mitochondrial oxidative phosphorylation. The aim of the present study was to elucidate the vasoactivity of NEN and the potential mechanisms. Isometric tension of rat mesenteric artery and thoracic aorta was recorded by using multi-wire myograph system. The protein levels were measured by using western blot techniques. Niclosamide ethanolamine (NEN) treatment relaxed phenylephrine (PE)- and high K+ (KPSS)-induced constriction, and pre-treatment with NEN inhibited PE- and KPSS-induced constriction of rat mesenteric arteries. In rat thoracic aorta, NEN also showed antagonism against PE- and KPSS-induced constriction. NEN induced increase of cellular ADP/ATP ratio in vascular smooth muscle cells (A10) and activated AMP-activated protein kinase (AMPK) in A10 cells and rat thoracic aorta. NEN-induced aorta relaxation was attenuated in AMPKα1 knockout (-/-) mice. SERCA inhibitors cyclopiazonic acid and thapsigargin, but not KATP channel blockers glibenclamide and 5-hydroxydecanoic acid, attenuated NEN-induced vasorelaxation in rat mesenteric arteries. NEN treatment increased cytosolic [Ca2+]i and depolarized mitochondrial membrane potential in vascular smooth muscle cells (A10). Niclosamide in non-salt form showed the similar vasoactivity as NEN in rat mesenteric arteries. Niclosamide ethanolamine inhibits artery constriction, indicating that it would be promising to be developed as an anti-hypertensive drug or it would induce vasodilation-related side effects when absorbed in vivo.

Mitochondrial uncoupler carbonyl cyanide m-chlorophenylhydrazone induces vasorelaxation without involving KATP channel activation in smooth muscle cells of arteries.

BACKGROUND AND PURPOSE: The effects and mechanisms of chemical mitochondrial uncouplers on vascular function have never been identified. Here, we characterized the effects of the typical mitochondrial uncoupler carbonyl cyanide m-chlorophenylhydrazone (CCCP) on vascular function in rat mesenteric arteries and aorta and elucidated the potential mechanisms. EXPERIMENTAL APPROACH: Isometric tension of mesenteric artery and thoracic aorta was recorded by using a multiwire myograph system. Protein levels were measured by western blot analyses. Cytosolic [Ca2+ ]i , mitochondrial ROS (mitoROS) and mitochondrial membrane potential of smooth muscle cells (A10) were measured by laser scanning confocal microscopy. KEY RESULTS: Acute treatment with CCCP relaxed phenylephrine (PE)- and high K+ (KPSS)-induced constriction of rat mesenteric arteries with intact and denuded endothelium. Pretreatment with CCCP prevented PE- and KPSS-induced constriction of rat mesenteric arteries with intact and denuded endothelium. Similarly, CCCP prevented PE- and KPSS-induced constriction of rat thoracic aorta. CCCP increased the cellular ADP/ATP ratio in vascular smooth muscle cells (A10) and activated AMPK in A10 cells and rat thoracic aorta tissues. CCCP-induced aorta relaxation was attenuated in AMPK α1 knockout (-/-) mice. SERCA inhibitors thapsigargin and cyclopiazonic acid (CPA) but not the KATP channel blocker glibenclamide partially inhibited CCCP-induced vasorelaxation in endothelium-denuded rat mesenteric arteries. CCCP increased cytosolic [Ca2+ ]i , mitoROS production and depolarized mitochondrial membrane potential in A10 cells. FCCP, the analogue of CCCP, had similar vasoactivity as CCCP in rat mesenteric arteries. CONCLUSIONS AND IMPLICATIONS: CCCP induces vasorelaxation by a mechanism that does not involve KATP channel activation in smooth muscle cells of arteries.

Azo polymeric micelles designed for colon-targeted dimethyl fumarate delivery for colon cancer therapy.

UNLABELLED: Colon-targeted drug delivery and circumventing drug resistance are extremely important for colon cancer chemotherapy. Our previous work found that dimethyl fumarate (DMF), the approved drug by the FDA for the treatment of multiple sclerosis, exhibited anti-tumor activity on colon cancer cells. Based on the pharmacological properties of DMF and azo bond in olsalazine chemical structure, we designed azo polymeric micelles for colon-targeted dimethyl fumarate delivery for colon cancer therapy. We synthesized the star-shape amphiphilic polymer with azo bond and fabricated the DMF-loaded azo polymeric micelles. The four-arm polymer star-PCL-azo-mPEG (sPCEG-azo) (constituted by star-shape PCL (polycaprolactone) and mPEG (methoxypolyethylene glycols)-olsalazine) showed self-assembly ability. The average diameter and polydispersity index of the DMF-loaded sPCEG-azo polymeric micelles were 153.6nm and 0.195, respectively. In vitro drug release study showed that the cumulative release of DMF from the DMF-loaded sPCEG-azo polymeric micelles was no more than 20% in rat gastric fluid within 10h, whereas in the rat colonic fluids, the cumulative release of DMF reached 60% in the initial 2h and 100% within 10h, indicating that the DMF-loaded sPCEG-azo polymeric micelles had excellent colon-targeted property. The DMF-loaded sPCEG-azo polymeric micelles had no significant cytotoxicity on colon cancer cells in phosphate buffered solution (PBS) and rat gastric fluid. In rat colonic fluid, the micelles showed significant cytotoxic effect on colon cancer cells. The blank sPCEG-azo polymeric micelles (without DMF) showed no cytotoxic effect on colon cancer cells in rat colonic fluids. In conclusion, the DMF-loaded sPCEG-azo polymeric micelles show colon-targeted DMF release and anti-tumor activity, providing a novel approach potential for colon cancer therapy. STATEMENT OF SIGNIFICANCE: Colon-targeted drug delivery and circumventing drug resistance are extremely important for colon cancer chemotherapy. Our previous work found that dimethyl fumarate (DMF), the approved drug by the FDA for the treatment of multiple sclerosis, exhibited anti-tumor activities on colon cancer cells (Br J Pharmacol. 2015 172(15):3929-43.). Based on the pharmacological properties of DMF and azo bond in olsalazine chemical structure, we designed azo polymeric micelles for colon-targeted dimethyl fumarate delivery for colon cancer therapy. We found that the DMF-loaded sPCEG-azo polymeric micelles showed colon-targeted DMF release and anti-tumor activities, providing a novel approach potential for colon cancer therapy.

Visible light photoswitching of conjugated polymer nanoparticle fluorescence.

Conjugated polymer nanoparticles doped with a reverse photochromic dye exhibit highly quenched fluorescence that can be reversibly activated by controlling the form of the photochrome with visible light.